Trial Outcomes & Findings for Clinical Medication Development for Bipolar Disorder and Alcohol Use Disorders (NCT NCT02582905)

Last Updated: 2024-10-09

Results Overview

The Timeline Follow Back (TLFB) - Alcohol is a clinician-completed assessment calendar that allows for an estimate of an individual's daily drinking habits over time (i.e., "prior 30 days" at baseline and "since last visit" during the study). Drinks per drinking day is calculated as the average number of standard drinks consumed, per each day indicated as a day during which alcohol was consumed, adjusted for the period of time being assessed (e.g., 30 days at baseline). Baseline-to-Exit Change in Drinks per Drinking Day (TLFB) was calculated as Drinks/Drinking Day (Exit) - Drinks/Drinking Day (Baseline), with negative scores indicating a decrease in the number of drinks per drinking day. The TLFB (Timeline Followback) is a method of assessment of alcohol consumption and is not a scale with minimum and maximum values.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

96 participants

Primary outcome timeframe

12 weeks

Results posted on

2024-10-09

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo Matching placebo given beginning at 1 capsule twice daily (BID) increasing to 2 capsules BID at week 1, 3 capsules BID at week 2, and 4 capsules BID at weeks 3-12. Placebo: Inactive ingredient matching the active comparators in appearance.	Citicoline Citicoline will be given beginning at 250 mg BID with an increase to 500 mg BID at week 1, 750 mg BID at week 2, and 1000 mg BID at weeks 3-12. Citicoline: Citicoline is an over-the-counter nutritional supplement that is used for neuroprotective effects. It is a naturally occurring neurochemical in the human body.	Pregnenolone Pregnenolone will be given beginning at 50 mg BID with an increase to 100 mg BID at week 1, 150 mg BID at week 2, and 250 mg BID at weeks 3-12. Pregnenolone: Pregnenolone is a naturally occurring neurosteroid that is synthesized from cholesterol in the adrenal glands and also in the brain. Pregnenolone produces other neuroactive steroids.
Overall Study STARTED	29	30	37
Overall Study COMPLETED	18	20	23
Overall Study NOT COMPLETED	11	10	14

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Clinical Medication Development for Bipolar Disorder and Alcohol Use Disorders

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=29 Participants Matching placebo given beginning at 1 capsule twice daily (BID) increasing to 2 capsules BID at week 1, 3 capsules BID at week 2, and 4 capsules BID at weeks 3-12. Placebo: Inactive ingredient matching the active comparators in appearance.	Citicoline n=30 Participants Citicoline will be given beginning at 250 mg BID with an increase to 500 mg BID at week 1, 750 mg BID at week 2, and 1000 mg BID at weeks 3-12. Citicoline: Citicoline is an over-the-counter nutritional supplement that is used for neuroprotective effects. It is a naturally occurring neurochemical in the human body.	Pregnenolone n=37 Participants Pregnenolone will be given beginning at 50 mg BID with an increase to 100 mg BID at week 1, 150 mg BID at week 2, and 250 mg BID at weeks 3-12. Pregnenolone: Pregnenolone is a naturally occurring neurosteroid that is synthesized from cholesterol in the adrenal glands and also in the brain. Pregnenolone produces other neuroactive steroids.	Total n=96 Participants Total of all reporting groups
Age, Continuous	48.00 years STANDARD_DEVIATION 8.98 • n=5 Participants	49.40 years STANDARD_DEVIATION 10.07 • n=7 Participants	47.35 years STANDARD_DEVIATION 10.11 • n=5 Participants	48.19 years STANDARD_DEVIATION 9.71 • n=4 Participants
Sex: Female, Male Female	12 Participants n=5 Participants	13 Participants n=7 Participants	18 Participants n=5 Participants	43 Participants n=4 Participants
Sex: Female, Male Male	17 Participants n=5 Participants	17 Participants n=7 Participants	19 Participants n=5 Participants	53 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	23 Participants n=5 Participants	26 Participants n=7 Participants	32 Participants n=5 Participants	81 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	5 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants	13 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	12 Participants n=5 Participants	15 Participants n=7 Participants	13 Participants n=5 Participants	40 Participants n=4 Participants
Race (NIH/OMB) White	16 Participants n=5 Participants	15 Participants n=7 Participants	21 Participants n=5 Participants	52 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants
YMRS	10.76 units on a scale STANDARD_DEVIATION 8.23 • n=5 Participants	10.20 units on a scale STANDARD_DEVIATION 7.01 • n=7 Participants	11.14 units on a scale STANDARD_DEVIATION 7.33 • n=5 Participants	10.73 units on a scale STANDARD_DEVIATION 7.45 • n=4 Participants
HRSD	14.62 units on a scale STANDARD_DEVIATION 6.14 • n=5 Participants	15.50 units on a scale STANDARD_DEVIATION 7.13 • n=7 Participants	13.46 units on a scale STANDARD_DEVIATION 6.91 • n=5 Participants	14.45 units on a scale STANDARD_DEVIATION 6.74 • n=4 Participants
HRSA	13.07 units on a scale STANDARD_DEVIATION 7.27 • n=5 Participants	13.80 units on a scale STANDARD_DEVIATION 6.67 • n=7 Participants	14.19 units on a scale STANDARD_DEVIATION 8.51 • n=5 Participants	13.73 units on a scale STANDARD_DEVIATION 7.54 • n=4 Participants
IDS-SR	26.00 units on a scale STANDARD_DEVIATION 14.38 • n=5 Participants	30.07 units on a scale STANDARD_DEVIATION 16.57 • n=7 Participants	26.92 units on a scale STANDARD_DEVIATION 14.46 • n=5 Participants	27.60 units on a scale STANDARD_DEVIATION 15.05 • n=4 Participants
CIWA-Ar	3.64 units on a scale STANDARD_DEVIATION 3.84 • n=5 Participants	3.40 units on a scale STANDARD_DEVIATION 2.85 • n=7 Participants	2.97 units on a scale STANDARD_DEVIATION 3.47 • n=5 Participants	3.31 units on a scale STANDARD_DEVIATION 3.38 • n=4 Participants
PACS	19.72 units on a scale STANDARD_DEVIATION 6.60 • n=5 Participants	19.31 units on a scale STANDARD_DEVIATION 7.90 • n=7 Participants	17.65 units on a scale STANDARD_DEVIATION 7.47 • n=5 Participants	18.79 units on a scale STANDARD_DEVIATION 7.33 • n=4 Participants
Metabolic Panel (AST)	23.82 U/L STANDARD_DEVIATION 10.59 • n=5 Participants	23.00 U/L STANDARD_DEVIATION 8.39 • n=7 Participants	24.38 U/L STANDARD_DEVIATION 13.73 • n=5 Participants	23.81 U/L STANDARD_DEVIATION 11.35 • n=4 Participants
Metabolic Panel (ALT)	22.96 U/L STANDARD_DEVIATION 14.99 • n=5 Participants	22.27 U/L STANDARD_DEVIATION 9.15 • n=7 Participants	24.51 U/L STANDARD_DEVIATION 24.71 • n=5 Participants	23.40 U/L STANDARD_DEVIATION 18.33 • n=4 Participants
Metabolic Panel (GGT)	52.85 U/L STANDARD_DEVIATION 73.46 • n=5 Participants	36.50 U/L STANDARD_DEVIATION 26.22 • n=7 Participants	37.46 U/L STANDARD_DEVIATION 27.07 • n=5 Participants	41.80 U/L STANDARD_DEVIATION 46.03 • n=4 Participants
Metabolic Panel (CDT)	57.39 mg/L STANDARD_DEVIATION 17.15 • n=5 Participants	58.04 mg/L STANDARD_DEVIATION 27.06 • n=7 Participants	58.72 mg/L STANDARD_DEVIATION 24.18 • n=5 Participants	58.12 mg/L STANDARD_DEVIATION 22.97 • n=4 Participants
TLFB (Drinks per Drinking Day)	9.15 Standard Drinks per Drinking Day STANDARD_DEVIATION 5.22 • n=5 Participants	8.01 Standard Drinks per Drinking Day STANDARD_DEVIATION 3.61 • n=7 Participants	7.35 Standard Drinks per Drinking Day STANDARD_DEVIATION 3.60 • n=5 Participants	8.11 Standard Drinks per Drinking Day STANDARD_DEVIATION 4.17 • n=4 Participants

PRIMARY outcome

Timeframe: 12 weeks

Population: Participants having at least one post-baseline visit.

Outcome measures

Outcome measures
Measure	Placebo n=29 Participants Matching placebo given beginning at 1 capsule twice daily (BID) increasing to 2 capsules BID at week 1, 3 capsules BID at week 2, and 4 capsules BID at weeks 3-12. Placebo: Inactive ingredient matching the active comparators in appearance.	Citicoline n=30 Participants Citicoline will be given beginning at 250 mg BID with an increase to 500 mg BID at week 1, 750 mg BID at week 2, and 1000 mg BID at weeks 3-12. Citicoline: Citicoline is an over-the-counter nutritional supplement that is used for neuroprotective effects. It is a naturally occurring neurochemical in the human body.	Pregnenolone n=37 Participants Pregnenolone will be given beginning at 50 mg BID with an increase to 100 mg BID at week 1, 150 mg BID at week 2, and 250 mg BID at weeks 3-12. Pregnenolone: Pregnenolone is a naturally occurring neurosteroid that is synthesized from cholesterol in the adrenal glands and also in the brain. Pregnenolone produces other neuroactive steroids.
Baseline-to-Exit Change in Drinks Per Drinking Day (TLFB)	-1.98 Standard Drinks per Drinking Day Standard Deviation 4.68	-2.82 Standard Drinks per Drinking Day Standard Deviation 3.84	-1.22 Standard Drinks per Drinking Day Standard Deviation 3.45

SECONDARY outcome

Timeframe: Study Month 30

Population: Planned interim analyses were to be conducted after 50% of participants (n = 99) were enrolled (phase 1) to determine whether to proceed with a two-arm trial in phase 2 (i.e., drop-the-loser). Only upon proceeding to phase 2 could this aim be tested. Due to low enrollment (total enrolled: n=96), the required data necessary to test this aim was not obtained. As such, the study remained in phase 1 (with three arms), and the adaptive drop-the-loser design was untested.

A two-phase adaptive drop-the-loser (DTL) design was incorporated. A planned interim analysis was to be conducted after 50% of participants (n = 99) had been enrolled (phase 1), in which both treatments were to be compared to placebo. Predetermined decision rules were to be applied for dropping a treatment failing to show clinically meaningful efficacy over placebo: (1) The trial will be stopped if neither active treatment appears to be effective (Cohen's d \< 0.25) and (2) The trial will continue to phase 2 (re-randomization) if there is evidence that at least one treatment is more effective than placebo. If both treatments were more effective, the trial was to continue with three arms.

Outcome measures

Outcome data not reported

Adverse Events

Placebo

Serious events: 3 serious events

Other events: 11 other events

Deaths: 0 deaths

Citicoline

Serious events: 2 serious events

Other events: 9 other events

Deaths: 0 deaths

Pregnenolone

Serious events: 4 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=29 participants at risk Matching placebo given beginning at 1 capsule twice daily (BID) increasing to 2 capsules BID at week 1, 3 capsules BID at week 2, and 4 capsules BID at weeks 3-12. Placebo: Inactive ingredient matching the active comparators in appearance.	Citicoline n=30 participants at risk Citicoline will be given beginning at 250 mg BID with an increase to 500 mg BID at week 1, 750 mg BID at week 2, and 1000 mg BID at weeks 3-12. Citicoline: Citicoline is an over-the-counter nutritional supplement that is used for neuroprotective effects. It is a naturally occurring neurochemical in the human body.	Pregnenolone n=37 participants at risk Pregnenolone will be given beginning at 50 mg BID with an increase to 100 mg BID at week 1, 150 mg BID at week 2, and 250 mg BID at weeks 3-12. Pregnenolone: Pregnenolone is a naturally occurring neurosteroid that is synthesized from cholesterol in the adrenal glands and also in the brain. Pregnenolone produces other neuroactive steroids.
Psychiatric disorders Panic Attack	3.4% 1/29 • Number of events 1 • 12 weeks. Specific adverse events (AEs) and symptoms reported by more than one participant are grouped by the specific AE or symptom. Symptoms that were reported only once are grouped by system (e.g., respiratory, GI, etc.). AEs of participants who presented the same symptom during their follow-up visit were included only once in reporting.	0.00% 0/30 • 12 weeks. Specific adverse events (AEs) and symptoms reported by more than one participant are grouped by the specific AE or symptom. Symptoms that were reported only once are grouped by system (e.g., respiratory, GI, etc.). AEs of participants who presented the same symptom during their follow-up visit were included only once in reporting.	0.00% 0/37 • 12 weeks. Specific adverse events (AEs) and symptoms reported by more than one participant are grouped by the specific AE or symptom. Symptoms that were reported only once are grouped by system (e.g., respiratory, GI, etc.). AEs of participants who presented the same symptom during their follow-up visit were included only once in reporting.
Psychiatric disorders Suicide attempts	3.4% 1/29 • Number of events 1 • 12 weeks. Specific adverse events (AEs) and symptoms reported by more than one participant are grouped by the specific AE or symptom. Symptoms that were reported only once are grouped by system (e.g., respiratory, GI, etc.). AEs of participants who presented the same symptom during their follow-up visit were included only once in reporting.	3.3% 1/30 • Number of events 1 • 12 weeks. Specific adverse events (AEs) and symptoms reported by more than one participant are grouped by the specific AE or symptom. Symptoms that were reported only once are grouped by system (e.g., respiratory, GI, etc.). AEs of participants who presented the same symptom during their follow-up visit were included only once in reporting.	0.00% 0/37 • 12 weeks. Specific adverse events (AEs) and symptoms reported by more than one participant are grouped by the specific AE or symptom. Symptoms that were reported only once are grouped by system (e.g., respiratory, GI, etc.). AEs of participants who presented the same symptom during their follow-up visit were included only once in reporting.
Psychiatric disorders Inpatient alcohol treatment	0.00% 0/29 • 12 weeks. Specific adverse events (AEs) and symptoms reported by more than one participant are grouped by the specific AE or symptom. Symptoms that were reported only once are grouped by system (e.g., respiratory, GI, etc.). AEs of participants who presented the same symptom during their follow-up visit were included only once in reporting.	3.3% 1/30 • Number of events 1 • 12 weeks. Specific adverse events (AEs) and symptoms reported by more than one participant are grouped by the specific AE or symptom. Symptoms that were reported only once are grouped by system (e.g., respiratory, GI, etc.). AEs of participants who presented the same symptom during their follow-up visit were included only once in reporting.	5.4% 2/37 • Number of events 2 • 12 weeks. Specific adverse events (AEs) and symptoms reported by more than one participant are grouped by the specific AE or symptom. Symptoms that were reported only once are grouped by system (e.g., respiratory, GI, etc.). AEs of participants who presented the same symptom during their follow-up visit were included only once in reporting.
Psychiatric disorders Overdose by partner on study medication	0.00% 0/29 • 12 weeks. Specific adverse events (AEs) and symptoms reported by more than one participant are grouped by the specific AE or symptom. Symptoms that were reported only once are grouped by system (e.g., respiratory, GI, etc.). AEs of participants who presented the same symptom during their follow-up visit were included only once in reporting.	0.00% 0/30 • 12 weeks. Specific adverse events (AEs) and symptoms reported by more than one participant are grouped by the specific AE or symptom. Symptoms that were reported only once are grouped by system (e.g., respiratory, GI, etc.). AEs of participants who presented the same symptom during their follow-up visit were included only once in reporting.	2.7% 1/37 • Number of events 1 • 12 weeks. Specific adverse events (AEs) and symptoms reported by more than one participant are grouped by the specific AE or symptom. Symptoms that were reported only once are grouped by system (e.g., respiratory, GI, etc.). AEs of participants who presented the same symptom during their follow-up visit were included only once in reporting.
Respiratory, thoracic and mediastinal disorders Pneumonia	0.00% 0/29 • 12 weeks. Specific adverse events (AEs) and symptoms reported by more than one participant are grouped by the specific AE or symptom. Symptoms that were reported only once are grouped by system (e.g., respiratory, GI, etc.). AEs of participants who presented the same symptom during their follow-up visit were included only once in reporting.	0.00% 0/30 • 12 weeks. Specific adverse events (AEs) and symptoms reported by more than one participant are grouped by the specific AE or symptom. Symptoms that were reported only once are grouped by system (e.g., respiratory, GI, etc.). AEs of participants who presented the same symptom during their follow-up visit were included only once in reporting.	2.7% 1/37 • Number of events 1 • 12 weeks. Specific adverse events (AEs) and symptoms reported by more than one participant are grouped by the specific AE or symptom. Symptoms that were reported only once are grouped by system (e.g., respiratory, GI, etc.). AEs of participants who presented the same symptom during their follow-up visit were included only once in reporting.
Metabolism and nutrition disorders hyponatremia	3.4% 1/29 • Number of events 1 • 12 weeks. Specific adverse events (AEs) and symptoms reported by more than one participant are grouped by the specific AE or symptom. Symptoms that were reported only once are grouped by system (e.g., respiratory, GI, etc.). AEs of participants who presented the same symptom during their follow-up visit were included only once in reporting.	0.00% 0/30 • 12 weeks. Specific adverse events (AEs) and symptoms reported by more than one participant are grouped by the specific AE or symptom. Symptoms that were reported only once are grouped by system (e.g., respiratory, GI, etc.). AEs of participants who presented the same symptom during their follow-up visit were included only once in reporting.	0.00% 0/37 • 12 weeks. Specific adverse events (AEs) and symptoms reported by more than one participant are grouped by the specific AE or symptom. Symptoms that were reported only once are grouped by system (e.g., respiratory, GI, etc.). AEs of participants who presented the same symptom during their follow-up visit were included only once in reporting.

Other adverse events

Additional Information

E. Sherwood Brown, MD PhD MBA

University of Texas Southwestern Medical Center

Phone: 214-645-6950

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place